Avtor/Urednik		Dolžan, V; Solyom, J; Fekete, G; Kovacs, J; Rakosnikova, V; Votava, F; Stopar-Obreza, M; Kržišnik, C; Battelino, Tadej
Naslov		Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congetinal adrenal hyperplasia
Tip		članek
Vir		Eur J Endocrinol
Vol. in št.		Letnik 153
Leto izdaje		2005
Obseg		str. 99-106
Jezik		eng
Abstrakt		Objective: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotypephenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. Design and methods: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. Results: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype-phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV CAH. (Abstract truncated at 2000 characters)
Deskriptorji		ADRENAL HYPERPLASIA, CONGENITAL STEROID 21-MONOOXYGENASE POINT MUTATION GENOTYPE PHENOTYPE GENE DELETION BLOTTING, SOUTHERN